DESCRIPTION (adapted from investigator's abstract and/or aims): The arthritis which develops in susceptible strains of mice immunized with either heterologous or autologous type II collagen has many similarities with human rheumatoid arthritis. These similarities include synovial pannus, joint edema and swelling, infiltration by lymphocytes, autoimmune reactions to type II collagen, formation of IgG (rheumatoid factor) which are MHC linked. Although susceptibility to this animal model of arthritis is clearly dependent on MHC genes, additional roles for non-MHC genes, in determining susceptibility, have been suggested by observations on the SWR mouse strain. This strain of mice has the H-2q MHC haplotype normally susceptible to the induction of CIA. It has since been shown that resistance to the development of the induction of CIA is correlated with the deletion of T cell receptor genes in H-2q mice. These observations, including the study of other types of T cell receptor deletions, indicate that there is a restrictive usage of T cell receptor V-beta genes in determining susceptibility to CIA. It is suggested that the deletion mutants are resistant to CIA because they cannot develop arthritogenic T cells and T cell dependent antibodies directed against epitopes on type II collagen in the joint. The applicant proposes to define the T cell population in arthritic joints in this model, i.e., is it oligoclonal or polyclonal, identify and sequence the specific T cell receptors within the joint and then develop an immunotherapy based on synthetic peptides corresponding to the disease associated T cell receptor V-beta gene sequences. The long-term goal is directed at experimental prevention and/or reversal of CIA in this animal model.